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3D Microfluidic Bone Tumor Microenvironment Comprised of Hydroxyapatite/Fibrin Composite.

Jungho Ahn1,2, Jungeun Lim1,2, Norhana Jusoh1,3

  • 1Department of Mechanical and Aerospace Engineering, Seoul National University, Seoul, South Korea.

Frontiers in Bioengineering and Biotechnology
|August 6, 2019
PubMed
Summary

Researchers engineered a bone-mimetic microenvironment using microfluidics to study cancer metastasis. They found hydroxyapatite (HA) concentration impacts tumor cell behavior and migration, offering insights for drug screening and understanding bone metastasis.

Keywords:
angiogenesiscancer metastasisfibrin matrixhydroxyapatitemicrofluidic platformtumor microenvironmentvascularized tumor

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Area of Science:

  • Biomaterials Science
  • Cancer Biology
  • Microfluidics

Background:

  • Bone is a common site for cancer metastasis due to its unique microenvironment.
  • The bone extracellular matrix (ECM), primarily hydroxyapatite (HA), influences tumor cell behavior and angiogenesis.
  • Understanding tumor-microenvironment (TME) interactions is crucial for developing effective cancer therapies.

Purpose of the Study:

  • To engineer a bone-mimetic microenvironment for studying cancer metastasis.
  • To investigate the impact of hydroxyapatite (HA) on tumor cell behavior and angiogenesis in a 3D TME model.
  • To develop a platform for drug screening and mechanistic studies of bone metastasis.

Main Methods:

  • Development of a microfluidic platform for culturing tumor cells in a 3D composite of HA and fibrin.
  • Creation of a bone metastasis TME model using colorectal (SW620) and gastric (MKN74) cancer cells.
  • Quantitative analysis of cell viability, proliferation, migration, and angiogenic sprout formation under varying HA concentrations and culture times.

Main Results:

  • HA concentration and culture time significantly affected cancer cell viability, proliferation, and cytoplasmic volume, demonstrating spatial and temporal TME heterogeneity.
  • Increased HA concentration inhibited migration of both SW620 and MKN74 cells.
  • High HA concentrations reduced the formation of angiogenic sprouts induced by paracrine factors from the TME.

Conclusions:

  • The engineered bone-mimetic microenvironment effectively models TME interactions relevant to bone metastasis.
  • Hydroxyapatite plays a significant role in modulating cancer cell behavior and angiogenesis in the bone metastatic niche.
  • This platform offers a valuable tool for drug screening and advancing the understanding of bone metastasis mechanisms.